Partial speed restrictions remain in place between Stawell and Great Western as works are undertaken to repair the stretch of road badly damaged by the ensuing fireball. 

Senior crash investigators have described the scene as 'the real horror of road trauma'.

Two people were killed and a 57-year-old man from Queensland is in a serious but stable condition in Melbourne's Alfred Hospital after a B-Double truck travelling west veered onto the wrong side of the road and collided with a semi-trailer travelling east.

A third vehicle, a car carrier then slammed into the rear of the semi-trailer travelling east, all vehicles erupting in flames.

The Western Highway between Stawell and Great Western was closed for most of yesterday as the Major Collision Investigation Unit (MCIU) began its investigations into the circumstances of the collision.

Members of the Disaster Victim Identification team from Melbourne assisted with efforts to identify and remove the bodies.

MCIU Detective Sergeant Darren Williams said it appeared the driver of the car carrier, who suffered significant burns to his body and airways, had no warning of the initial smash as he rounded the bend in the road at Black Range.

"Our investigation, especially when you're dealing with trucks, centres around fatigue. We'll obviously go back and see whether fatigue was an issue in relation to this crash," he said.

One of the trucks was carrying household products, including aerosol cans, while another was transporting cars.

Det Sgt Williams expected investigators to be on site for much of yesterday, with the rehabilitation of the road and surrounding area to take considerably longer.

"The road is badly burnt, charred, there is so much debris. It's just one of those things, this is the real horror of road trauma," he said.

"Walking through that scene you just... people just don't have any realisation of what it's like. I mean this is like bushfire stuff, that is just how hot this fire was.

The inferno sparked by the explosion spread to near-by grassland and burned for several hours before fire crews were able to bring it under control just after 6am yesterday.

"Just before Christmas, yes we have 20 days to go and two people who aren't going to make it," Det Sgt Williams said.

Daily about 1600 heavy vehicle trucks and another 5000 motor vehicles use the main arterial at Stawell that links Melbourne with Adelaide.

Northern Grampians Shire Mayor, Cr Kevin Erwin who is also the chairman of the Western Highway Action Committee has expressed his sadness at the tragedy.

"Words really can't describe it. This is going to make for a sad time for many people over Christmas," he said.

Cr Erwin said when he meets with State Transport Minister Terry Mulder next Tuesday, he will be looking for a guarantee of funding for the long awaited duplication of the Western Highway between Stawell and Buangor.

"This is something that has been on the drawing board for at least 20 years. We have the plan for the Buangor to Stawell section we just need the funding.

"If we get the contribution we need from both the state and federal governments work could commence by summer next year.

"We realise money is tight but the State and Federal governments need to make this money available," he said.

Det Sgt Williams said the message from police remains clear, and the same.

"Our message is to stay alert, stay alive and be aware of your surroundings. Stop if you're fatigued," he said.

"Drive carefully, don't drink and drive, and don't speed. If you obey all these things, you won't get into trouble and you won't get into crashes."

Police will prepare a report on Wednesday's crash for the Coroner.